STAT3 and STAT5 Activation in Solid Cancers

Abstract

The Signal Transducer and Activator of Transcription (STAT)3 and 5 are activated by many cytokine receptors to regulate specific gene expression and mitochondrial functions. Their role in cancer is largely context dependent as they can both act as oncogenes and tumor suppressors. We review here the role of STAT3/5 activation in solid cancers and summarize their association to survival in cancer patients. The molecular mechanisms that underpins the oncogenic activity of STAT3/5 signaling includes the regulation of genes that control cell cycle, cell death, inflammation and stemness. In addition, STAT3 mitochondrial functions are required for transformation. On the other hand, several tumor suppressor pathways act on or are activated by STAT3/5 signaling including the p19ARF/p53 pathway, tyrosine phosphatases, suppressor of cytokine signaling 1 and 3, the sumo ligase PIAS3, the E3 ubiquitin ligase TMF/ARA160 and the miRNAs miR-124 and miR-1181. Cancer mutations and epigenetic alterations may alter the balance between prooncogenic and tumor suppressor activities associated to STAT3/5 signaling explaining their context dependent association to tumor progression both in human cancers and animal models.

Signal transducer and activator of transcription family is a prognostic marker associated with immune infiltration in endometrial cancer

“…STAT family members can act as both oncogenes and tumor suppressors. Therefore, the use of the STAT family as a diagnostic and prognostic basis requires careful consideration of each specific cancer type and the characteristics of each patient 8,29 …”

Cross‐Talk between Oxidative Stress and m6A RNA Methylation in Cancer

“…Oncogenes also mediate ROS production by regulating NOXs expression. Signal transducer and activator of transcription 3 (STAT3) increases NOX4 expression [80]; mutant KRAS activates NOX1 and downregulates antioxidant enzymes, including SOD2, catalase, and Prxs [81,82]; and Ras-related C3 botulinum toxin subunit 1 (Rac1) can stimulate the production of mitochondrial superoxide and participate in the assembly and activation of NOX1 and NOX3 [83][84][85][86]. Tumor suppressor p53 and forkhead box O (FOXO) family transcription factors can prevent oxidative stress by inducing the expression of antioxidant genes.…”

Activated STAT3 Could Reduce Survival in Patients with Esophageal Squamous Cell Carcinoma by Up-regulating VEGF and Cyclin D1 Expression

“…p-STAT3 is able to increase the expression levels of certain target genes, including vascular endothelial growth factor (VEGF), Cyclin D1 and Bcl-xL, etc [9][10][11][12]. STAT3 constitutively activation is frequently observed in cancers, including lung cancer, liver cancer, gastric cancer and renal cell carcinoma [13]. Increasing number of studies show that STAT3 may serve as one of the oncogenic critical factors and is associated with a poor prognosis in certain types of cancer.…”

“…Increasing number of studies show that STAT3 may serve as one of the oncogenic critical factors and is associated with a poor prognosis in certain types of cancer. For instance, it has been reported that elevated STAT3 expression is associated with poor prognosis in gastric cancer, lung cancer and live cancer [13]. Additionally, STAT3 has been revealed to be crucial involved in cancer cell proliferation, invasion, migration and apoptosis [14,15].…”